Endocrine Connections最新文献

{"title":"Factors affecting the quality of life of adults living with congenital adrenal hyperplasia: a qualitative study of lived experience.","authors":"K Lynette James, Nicola Parkin, Sue Elford, Christine McKnight, Rhiannon Phillips, Timothy Pickles, S Faisal Ahmed, Nils Krone, Sofia Llahana, Michael W O'Reilly, Jeremy W Tomlinson, D Aled Rees","doi":"10.1530/EC-26-0033","DOIUrl":"10.1530/EC-26-0033","url":null,"abstract":"<p><strong>Objective: </strong>Congenital adrenal hyperplasia (CAH) is a genetic condition caused by enzymatic defects of adrenal steroidogenesis. The physical manifestations of CAH are well recognised, but the effects on health-related quality of life (HRQoL) are unclear. We sought to explore the factors impacting the HRQoL of individuals with CAH.</p><p><strong>Design: </strong>Phenomenological qualitative study of lived experience.</p><p><strong>Methods: </strong>In-depth, timeline-assisted, semi-structured interviews were undertaken virtually with participants recruited via the Living with CAH patient support group. Participants, purposively selected until data saturation, were adults (≥18 years) with CAH and parents or partners of adults with CAH. Interviews were audio-recorded, transcribed verbatim, and analysed using framework analysis.</p><p><strong>Results: </strong>Twenty-three participants were interviewed (20 classic, 1 non-classic, and 2 mothers). Most participants (n = 19) were female. CAH has a profound physical, psychological, and psychosocial impact on individuals. The psychological well-being of women was compromised by trauma from childhood medical examinations and a lack of agency in treatment decisions. Poor self-esteem, shame, and negative body image impaired female social functioning. Female sexual dysfunction from genital malformation or surgery and psychosexual issues negatively impacted intimate relationships. Fertility and reproductive choices were a concern to both sexes. Complex family dynamics with dependent relationships were evident.</p><p><strong>Conclusion: </strong>This study identified a breadth of factors impacting HRQoL in CAH - domains overlooked by an existing measure that predominantly focuses on physical symptoms. Further work is needed to develop a sensitive, comprehensive disease-specific HRQoL measure that reflects the lived experience of individuals with CAH to facilitate delivery of patient-centred care and improved patient outcomes.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13188198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The IGF signaling axis in thyroid cancer: biological complexity and therapeutic challenges.","authors":"Youyun Peng, Shaojie Xu, Hanning Li, Xingrui Li, Yaying Du","doi":"10.1530/EC-26-0144","DOIUrl":"10.1530/EC-26-0144","url":null,"abstract":"<p><p>Dysregulation of the insulin-like growth factor (IGF) axis plays an important role in thyroid cancer progression, dedifferentiation, and therapeutic resistance. While most differentiated thyroid cancers have favorable outcomes, a clinically significant subset develops aggressive behavior or becomes radioiodine (RAI) refractory, for which effective treatments remain limited. Aberrant activation of IGF ligands, IGF-1 receptor (IGF-1R), insulin receptor isoforms (especially IR-A), and IGF-binding proteins (IGFBPs) enhances oncogenic signaling through the PI3K/AKT and MAPK pathways and disrupts differentiation programs essential for iodine handling. Emerging evidence supports an IGF-2/IR-A-dominant autocrine circuit as a feature of aggressive and RAI-refractory disease, highlighting its potential relevance for biomarker-driven patient stratification. However, the clinical translation of IGF-axis targeting in thyroid cancer remains limited, and IGF-1R-directed monotherapies have shown only modest efficacy owing to signaling redundancy, adaptive resistance, metabolic toxicities, and the lack of validated predictive biomarkers for patient selection. Consequently, current translational efforts increasingly emphasize rational combination strategies, targeted delivery platforms, and molecular imaging approaches. This review summarizes key mechanistic and translational insights into IGF signaling in thyroid cancer and discusses how IGF-axis modulation may be integrated into precision oncology strategies for advanced disease.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13188199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurophysin-I dynamics upon different pituitary provocation tests in healthy participants.","authors":"Andi Nikaj, Cihan Atila, Deborah Rudin, Dino Luethi, Clara O Sailer, Bettina Winzeler, Sandrine A Urwyler, Julie Refardt, Matthias E Liechti, Mirjam Christ-Crain","doi":"10.1530/EC-25-0929","DOIUrl":"10.1530/EC-25-0929","url":null,"abstract":"<p><strong>Background: </strong>Oxytocin (OXT) is known for its role in regulating social behavior, such as emotion recognition and bonding. The evidence for clinically relevant OXT deficiency is constantly increasing, but the measurement of OXT is challenging. In contrast, neurophysin-I (NP-I), the carrier protein of OXT and co-released equimolarly, is a stable surrogate biomarker for OXT. This study evaluated OXT and NP-I levels upon four different pituitary provocation tests.</p><p><strong>Design: </strong>Secondary analysis of four interventional diagnostic trials at the University Hospital Basel, Switzerland.</p><p><strong>Methods: </strong>Sixty-six participants underwent a pituitary provocation test, 11 the hypertonic saline test, 20 the arginine infusion test, 25 the oral macimorelin test, and 10 the glucagon injection test. Plasma NP-I and OXT were measured at baseline and once the plasma sodium level reached ≥150 mmol/L for the hypertonic saline, after 60 min for the arginine infusion, after 60, 120, and 180 min for the glucagon injection, and after 45 min for the oral macimorelin test. The primary outcome was change from baseline to maximally stimulated NP-I levels.</p><p><strong>Results: </strong>Median (IQR) NP-I plasma levels increased minimally in response to hypertonic saline (baseline: 55 pM, stimulated: 59 pM, relative median change of -8% (-16, +9)) and significantly to glucagon injection (baseline: 82 pM, stimulated: 94 pM, relative median change of +18% (+7, +28)). Median OXT levels showed similar trends in response to hypertonic saline (baseline: 0.36 pg/mL (0.27, 0.45), stimulated: 0.48 pg/mL (0.43, 0.59), relative median change of +22% (-15, +96)) and to glucagon injection (baseline: 82.7 pg/mL (62.3, 94.3), stimulated: 93.4 pg/mL (87.2, 121), relative median change of +25% (+6, +59). Neither the NP-I plasma levels nor OXT levels increased upon arginine infusion and oral macimorelin.</p><p><strong>Conclusion: </strong>NP-I showed minimal responses to pituitary provocation tests, paralleling OXT dynamics. These findings highlight NP-I's potential as a reliable and technically robust surrogate biomarker for OXT activity, warranting further evaluation in clinical and experimental settings.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13188200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"'Glucocorticoids, Cushing's syndrome and cellular senescence: a mechanistic link to metabolic ageing'.","authors":"Cintia M Santillan, Maha Abbas, Salvador Macip, Felicia A Hanzu","doi":"10.1530/EC-26-0197","DOIUrl":"10.1530/EC-26-0197","url":null,"abstract":"<p><p>Glucocorticoids are key regulators of immune, stress, and inflammatory responses, as well as of multiple metabolic pathways throughout life, and they play an anabolic role in tissue and organ development. Chronic glucocorticoid excess, whether due to endogenous Cushing's syndrome, long-term pharmacological treatment, or persistent stress, induces tissue-specific alterations that closely resemble those seen during physiological ageing. These shared changes include loss of tissue regenerative capacity, altered body composition, impaired glucose and lipid homeostasis, and increased cardiovascular and neuropsychiatric vulnerability. Emerging evidence indicates that glucocorticoid excess can promote cellular senescence, amplify pro-inflammatory signalling, and disrupt inter-organ communication, thereby accelerating a state of metabolic ageing. This review synthesises current clinical and experimental data linking glucocorticoid excess with cellular senescence in key metabolic organs and systems, including adipose tissue, skeletal muscle, liver, bone, the cardiovascular system, and the brain. Particular emphasis is placed on chronic neoplastic hypercortisolism as a human model, while also considering prolonged pharmacological glucocorticoid exposure and sustained stress as more prevalent, subclinical sources of hormonal overload. By integrating these lines of evidence, we outline the emerging concept of glucocorticoid-driven metabolic ageing and highlight potential mechanistic targets along the glucocorticoid axis and within senescence pathways. A better understanding of these mechanisms may inform strategies to prevent or mitigate age-related metabolic and cardiovascular complications in patients with Cushing's syndrome, in individuals exposed to long-term glucocorticoid therapy, and in the broader ageing population.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13178434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147638188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the relationship between microplastic exposure and bone health.","authors":"Apostolos I Gogakos, Stergios A Polyzos, Dimitrios A Anastasilakis, Athanasios D Anastasilakis","doi":"10.1530/EC-26-0187","DOIUrl":"10.1530/EC-26-0187","url":null,"abstract":"<p><p>The ubiquity of microplastics and nanoplastics (or microplastic and nanoplastic particles, collectively MNPs) in the modern environment has led to the detection of polymer particles and polymer-associated chemicals repeatedly within human tissues and fluids, inevitably raising concern for long-term effects on organ systems, including the skeleton. Accumulated evidence over the past decade implicates MNPs and plastic-associated endocrine-disrupting chemicals (EDCs), such as phthalates and bisphenols, in pathways central to bone homeostasis and in direct cellular toxicity to bone cells. Epidemiological data that directly link MNP burden to osteoporosis or fractures in humans remain scarce; by contrast, multiple human biomonitoring studies of phthalates, bisphenol analogs, and other EDCs report associations with lower bone mineral density or with surrogate markers of bone turnover. Preclinical studies suggest plausible causal routes by which MNPs could affect bone strength. This narrative review synthesizes current human-relevant data on exposure, tissue presence, epidemiology, and mechanisms; highlights critical gaps; and proposes priorities for research and clinical surveillance.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13178428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spectrum and genotype-phenotype correlation of NR5A1 variants in 46,XY DSD: a systematic review and meta-analysis.","authors":"Renata T Dallago, Rafael Loch Batista, Sorahia Domenice, Vania Dos Santos Nunes-Nogueira, Berenice Bilharinho Mendonca","doi":"10.1530/EC-25-0783","DOIUrl":"10.1530/EC-25-0783","url":null,"abstract":"<p><strong>Context: </strong>NR5A1 encodes steroidogenic factor 1, a master regulator of adrenal and gonadal development. Pathogenic NR5A1 variants are among the most common genetic findings in 46,XY differences of sex development (DSD), yet the broad phenotypic spectrum remains incompletely defined.</p><p><strong>Objective: </strong>This study aims to establish pooled estimates of key clinical outcomes and to clarify whether variant type predicts phenotype, pubertal course, or gender transition in NR5A1-related 46,XY DSD.</p><p><strong>Methodology: </strong>MEDLINE, Embase, and HGMD were systematically searched. Two reviewers independently screened, extracted, and appraised studies following the methodology of the Joanna Briggs Institute. Ninety-eight studies (312 individuals) were included; 35 series with ≥3 cases entered meta-analysis. Across studies, 85% presented atypical external genitalia and 15% female-like genitalia; sex of rearing was female in 54%. Spontaneous puberty occurred in 82% (95% CI: 45-96), and adrenal insufficiency in only 1.6%. All reported gender transitions were female to male (10%, 95% CI: 5-21). Missense variants represented 54%. Meta-regressions revealed no association between variant class and genital phenotype (odds ratio (OR): 1.25) or between phenotype and gender transition (OR: 0.46).</p><p><strong>Conclusion: </strong>NR5A1-related 46,XY DSD is a dynamic condition with high rates of spontaneous virilisation (82%) and minimal adrenal involvement (1.6%). The absence of clear genotype-phenotype correlations and the occurrence of female-to-male gender reassignment support a conservative, longitudinal, patient-centred model of care. Given the unpredictability of individual outcomes, the quantitative estimates from this review support a shift towards evidence-based, longitudinal care that prioritises patient autonomy by deferring irreversible decisions.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13178433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147688752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and external validation of a parsimonious endocrine-metabolic model for 12-month pregnancy prediction in women with polycystic ovary syndrome (PCOS).","authors":"Sifu Ha, Lina Liu, Jian Li, Haixin Yu, Hong Liu, Lin Ma, Xin Liu","doi":"10.1530/EC-26-0049","DOIUrl":"10.1530/EC-26-0049","url":null,"abstract":"<p><strong>Background: </strong>Women with polycystic ovary syndrome (PCOS) exhibit diverse reproductive and metabolic phenotypes, complicating short-term pregnancy counseling. We developed and externally validated a pragmatic model to predict clinical pregnancy within 12 months.</p><p><strong>Methods: </strong>This retrospective cohort study utilized data from Center A (development) and Center B (validation). Predictors included routinely available anthropometric, reproductive endocrine, metabolic, and treatment markers. We developed a multivariable logistic regression model, evaluating discrimination (AUC and precision-recall), calibration (decile-based plots), and clinical utility via decision curve analysis (DCA). Clinical pregnancy, confirmed by ultrasonography, served as the reference standard. A web-based calculator was created for bedside risk estimation.</p><p><strong>Results: </strong>In the development cohort (n = 315; 167 pregnancies), the final model retained age, anti-Müllerian hormone (AMH), LH/FSH ratio, assisted reproductive treatment, HOMA-IR, and homocysteine. The model demonstrated good discrimination (AUC = 0.813) and remained robust after internal validation (AUC = 0.800; AUPRC = 0.823). Calibration showed strong agreement between predicted and observed probabilities, despite minor deviations at higher risk levels. DCA indicated higher net benefit compared to 'treat-all' or 'treat-none' strategies across relevant thresholds. External validation confirmed acceptable discrimination (AUC = 0.759), with modest calibration attenuation (slope = 0.681; intercept = -0.019).</p><p><strong>Conclusion: </strong>This endocrine-metabolic model provides individualized 12-month pregnancy predictions for women with PCOS, demonstrating validated discrimination and decision-analytic utility. While the web calculator facilitates clinical implementation, local recalibration is recommended to ensure accuracy across different populations.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13150336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of basal thyroid function with clinical outcomes in patients with recurrent or metastatic nasopharyngeal carcinoma treated with PD-L1 inhibitor KL-A167: a multicenter post hoc analysis.","authors":"Keliang Chen, Haohan Fan, Shihong Xu, Jiacheng Li, Junyou Ge, Yan Qing, Youneng Wei, Yuping Xie, Xingchen Peng","doi":"10.1530/EC-26-0083","DOIUrl":"10.1530/EC-26-0083","url":null,"abstract":"<p><strong>Objective: </strong>While thyroid dysfunction during PD-L1 inhibitor therapy correlates with efficacy in recurrent/metastatic nasopharyngeal carcinoma, the prognostic value of basal thyroid function remains unclear. This study investigated the relationship between baseline serum thyroid-stimulating hormone (TSH) and clinical outcomes.</p><p><strong>Methods: </strong>We conducted a multicenter, retrospective analysis of 153 recurrent/metastatic nasopharyngeal carcinoma (R/M NPC) patients from a prospective phase 2 trial of the PD-L1 inhibitor KL-A167. Patients were stratified by baseline TSH levels. Multivariate Cox and logistic regression models were used to analyze progression-free survival (PFS), overall survival (OS), and objective response rate (ORR).</p><p><strong>Results: </strong>High basal TSH (n = 58) was independently associated with significantly prolonged OS (HR 0.56, 95% CI: 0.36-0.88; P = 0.011) and PFS (HR 0.60, 95% CI: 0.41-0.87; P = 0.008) compared to the low/normal TSH group (n = 95). Although ORR was numerically higher in the high TSH group (27.6 vs 17.9%), the difference was not statistically significant (P = 0.23). Subgroup analyses indicated consistent benefits across most clinical strata. Thyroid immune-related adverse events occurred in 32/153 (20.9%), similarly between groups (20.7 vs 21.1%, P = 0.957), and were not significantly associated with either OS (HR 0.65, 95% CI: 0.38-1.11, P = 0.117) or PFS (HR 0.88, 95% CI: 0.54-1.44, P = 0.613) by time-varying Cox regression.</p><p><strong>Conclusion: </strong>Elevated basal TSH levels are independently associated with improved survival in R/M NPC patients receiving KL-A167. Baseline TSH may serve as a simple, noninvasive biomarker for risk stratification and personalizing immunotherapy in this population.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13150324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adiponectin modulates the diurnal hepatic transcriptome and energy metabolism in male mice.","authors":"Misa Hirose, Enrique Calvo, Violetta Pilorz, Meike Kaehler, Ingolf Cascorbi, Inga Nagel, Leonardo Vinicius Monteiro de Assis, Henrik Oster","doi":"10.1530/EC-26-0016","DOIUrl":"10.1530/EC-26-0016","url":null,"abstract":"<p><p>Adiponectin is an adipocyte-derived hormone with insulin-sensitizing and lipid-lowering effects. Its expression and circulating levels show pronounced variation across the day, which opens the possibility that adiponectin influences metabolic programs in target tissues, such as the liver in a time-of-day dependent manner. To test this, we compared liver circadian transcriptome profiles (with sampling at 4-h intervals) between adiponectin-deficient (ADQ-KO) and wild-type (ADQ-WT) mice. Adiponectin loss led to tonic (i.e. time-independent) transcriptional changes in the liver with 1,393 differentially expressed genes (518 up- and 875 downregulated). These included upregulation of chromatin and RNA processing pathways and downregulation of immune and mitochondrial metabolic genes. At the same time, circadian analysis identified a marked reprogramming of transcriptome rhythms in ADQ-KO livers with changes in MESOR (n = 3,369 transcripts), amplitude (n = 386), and phase of gene expression (n = 603). Genes associated with mitochondrial respiration and fatty acid metabolism showed reduced rhythm amplitude and MESOR, whereas glycolytic genes exhibited increased MESOR. One of the identified adiponectin candidate targets and a regulator of hepatic metabolism, Hif1a, was further studied by functional assays in murine hepatocytes. Pharmacological adiponectin receptor activation promoted glycolysis and mitochondrial respiration under normoxia, but these effects were attenuated under hypoxia mimicry, consistent with HIF1a-dependent interference. These findings suggest adiponectin as a regulator of liver circadian metabolism, modulating both the timing and magnitude of energy-related gene expression programs, potentially in part through a HIF1a-mediated mechanism.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147688826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical characteristics and management of PD-1/PD-L1 inhibitor-induced secondary adrenal insufficiency.","authors":"Na Li, Tianfu Liang, Hanbing Xie, Ye Niu","doi":"10.1530/EC-26-0079","DOIUrl":"10.1530/EC-26-0079","url":null,"abstract":"<p><strong>Graphical abstract: </strong></p><p><strong>Abstract: </strong>Programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors significantly improve outcomes in multiple malignancies; however, they can induce immune-related endocrine adverse events, such as secondary adrenal insufficiency (SAI), a rare but potentially severe complication. We aimed to systematically analyze the clinical characteristics, changes in endocrine function, and treatment outcomes of SAI induced by PD-1/PD-L1 immune checkpoint inhibitors. This single-center retrospective study included 75 patients with tumors diagnosed with SAI following PD-1/PD-L1 inhibitor therapy. Clinical data were collected via electronic medical records, and clinical characteristics and prognosis data were analyzed using descriptive statistical methods. SAI occurred at any cycle during immunotherapy, with a median onset of 5.70 months. Clinically, fatigue was the most common symptom (80.0%), followed by loss of appetite (26.7%) and nausea (9.3%). Endocrine function assessments revealed that severe hypothalamic-pituitary-adrenal (HPA) axis impairment occurred in all patients; thyroid function abnormalities occurred in 34.7% of patients, with PD-1/PD-L1 inhibitor-related hypothyroidism accounting for 88.5%, of which 65.2% of hypothyroidism cases preceded SAI diagnosis. Central hypothyroidism (4.0%) and gonadal involvement (1.3%) were relatively rare; treatment outcome analysis showed that only 8.3% (1/12) of patients receiving high-dose glucocorticoid therapy recovered HPA axis function; 98.7% (74/75) of patients on long-term glucocorticoid replacement therapy tolerated subsequent anti-tumor treatment, and 59.5% maintained the regimen, including ICIs. These findings reveal the need to enhance endocrine monitoring during immunotherapy, prioritize HPA axis evaluation in patients with thyroid dysfunction, and promptly initiate standardized glucocorticoid replacement therapy upon SAI diagnosis to ensure continuity of anti-tumor treatment.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13150331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147671533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}